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dc.contributor.authorWilliams-Gray, Carolineen
dc.contributor.authorWijeyekoon, Ruwanien
dc.contributor.authorYarnall, Alison Jen
dc.contributor.authorLawson, Rachel Aen
dc.contributor.authorBreen, David Pen
dc.contributor.authorEvans, Jonathan Ren
dc.contributor.authorCummins, Gemma Aen
dc.contributor.authorDuncan, Gordon Wen
dc.contributor.authorKhoo, Tien Ken
dc.contributor.authorBurn, David Jen
dc.contributor.authorBarker, Rogeren
dc.contributor.authoron, behalf of the ICICLE-PD study groupen
dc.identifier.citationMovement Disorders 2016.en
dc.description.abstract$\textbf{Background:}$ The immune system is a promising therapeutic target for disease modification in Parkinson’s disease (PD), but appropriate immune-related biomarkers must be identified to allow patient stratification for trials and tracking of therapeutic effects. The objective of this study was to investigate whether immune markers in peripheral blood are candidate prognostic biomarkers through determining their relationship with disease progression in PD. $\textbf{Methods:}$ Serum samples were collected in incident PD cases and age-matched controls. Subjects were clinically evaluated at baseline and 18 and 36 months. Ten cytokines and C-reactive protein were measured, with data reduction using principal-component analysis, and relationships between component scores and motor (MDS Unified Parkinson’s Disease Rating Scale — part 3) and cognitive (Mini Mental State Examination [MMSE]) measures of disease severity/progression were investigated. $\textbf{Results:}$ TNF-$\alpha$, IL1-$\beta$, IL-2, and IL-10 were higher in PD (n = 230) than in controls (n = 93), $P$ $\leq$ 0.001). Principal-component analysis of log-transformed data resulted in a 3-component solution explaining 51% of the variance. Higher “proinflammatory” and lower “antiinflammatory” component scores were associated with more rapid motor progression over 36 months ($P$ < 0.05), and higher “proinflammatory” component scores were associated with lower MMSE at all times ($P$ < 0.05). Multiple linear regression analysis with adjustment for covariates confirmed “anti-inflammatory” component score was the strongest predictor of slower motor progression ($\beta$ = -0.22, $P$ = 0.002), whereas proinflammatory cytokines were associated with lower baseline MMSE ($\beta$ = -0.175, $P$ = 0.007). $\textbf{Conclusions:}$ Serum immune marker profile is predictive of disease progression in PD and hence a potential prognostic biomarker. However, interventional trials are needed to clarify whether peripheral immune changes causally contribute to the progression of PD.
dc.description.sponsorshipThis work was funded by grants from Parkinson’s UK (J-0802), the Academy of Medical Sciences, UK, the Rosetrees Trust, the Stevenage Biosciences Catalyst and the Lockhart Parkinson’s Disease Research Fund. The research was also supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Unit (Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University) and the NIHR Cambridge Biomedical Research Centre (Cambridge University Hospitals NHS Trust/University of Cambridge)
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.subjectParkinson’s diseaseen
dc.subjectimmune markersen
dc.subjectlongitudinal studiesen
dc.titleSerum Immune Markers and Disease Progression in an Incident Parkinson’s Disease Cohort (ICICLE-PD)en
dc.title.alternativeSerum immune markers and PD progressionen
dc.description.versionThis is the final version of the article. It first appeared from Wiley via
prism.publicationNameMovement Disordersen
dc.contributor.orcidWilliams-Gray, Caroline [0000-0002-2648-9743]
dc.contributor.orcidBarker, Roger [0000-0001-8843-7730]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idAcademy of Medical Sciences (unknown)
pubs.funder-project-idWELLCOME TRUST (103838/Z/14/Z)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idMedical Research Council (MC_U105597119)
cam.orpheus.successThu Jan 30 12:55:25 GMT 2020 - The item has an open VoR version.*

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International